Impact of Anemia & Hemolysis in Sickle Cell Disease - Episode 4
Sophie M. Lanzkron, MD, MHS, and Jeffrey D. Lebensburger, DO, MSPH, review the underlying pathophysiology of acute multisystem organ failure and resulting cerebrovascular and neurologic complications associated with sickle cell disease.
Sophie M. Lanzkron, MD, MHS: Multisystem organ failure is a difficult and challenging problem. The acute development of multisystem organ failure is driven probably by fat embolization. Patients have a big bony infarct and will present with pain in their typical locations, but it’s much more severe than what they’ve had in the past. You have this bony infarct, and fat gets released from the marrow and goes to multiple places and organs. If it just goes to your lungs, you might just have acute chest syndrome. But if it goes to your lung, brain, and kidneys, then we think those folks have multisystem organ failure. It’s been defined as having 3 organs affected and is a life-threatening complication of the disease that requires rapid identification and often exchange transfusions to help the patient survive these episodes.
Jeffrey D. Lebensburger, DO, MSPH: There’s been a longstanding question of this hemolytic phenotype of patients with sickle cell disease versus a vaso-occlusive set of patients. There are certain organs that are definitely going to be damaged by a hemolytic event. For example, in the kidney, we know that during hemolysis, free hemoglobin is presented to the proximal tubule and can damage that proximal tubule. Second, it would be in the heart. An acute hemolytic patient who has suffered from longstanding chronic anemia and longstanding hemolysis is going to be more at risk for developing pulmonary hypertension. In the brain, we know that anemia places patients at increased risk for having a stroke. Epidemiologic studies have shown that anemia is a risk factor for organ pathophysiology.
The CNS [central nervous system] is one of the major organs where we find damage in pediatrics, and it can happen from a very early age, and it can be life limiting. One issue we need support with is making sure our patients get a stroke screening every year. It’s been demonstrated by [Julie] Kanter, [MD,] and others that we have the technology to identify patients at risk for stroke, yet the implementation of stroke screening can be decreased in some settings. It’s vital that all of our patients starting at 2 years of age get stroke screening with a transcranial Doppler. Other things we need to be doing include looking for neuropsychological complications. [Data have shown] that CNS deficits occur and these lead to abnormal outcomes in terms of cognitive success at school and other neurocognitive outcomes. It’s very important that we screen our patients for neurocognitive deficits and work hard to make sure our patients get the necessary skills that they need at school for the support to develop the appropriate life skills.
Second, what happens in the brain is, due to this anemia, a decrease in arterial oxygen content. Melanie Fields, [MD]’s work shows that in patients with sickle cell disease there’s decreased arterial oxygen saturation in the brain. The brain has to develop mechanisms to increase cerebral blood flow. If there’s not enough cerebral blood flow and not enough oxygen delivery, then our patients are at risk for either an overt stroke or a silent stroke. Most of our patients with sickle cell are going to have this elevated cerebral blood flow, and if they can maintain perfusion in the brain, they can maintain oxygen content. But in situations of stress, whether it’s fever or when less oxygen content is being delivered to the brain, we put the brain at risk for having an acute event, whether it’s a silent cerebral infarct or an acute stroke. Constantly, we need to be monitoring our patients to make sure we put them at low risk, and strategies to improve oxygen delivery to the brain are vital. Finally, we have patients without enough oxygen delivery who have to develop new ways to get oxygen to the brain. That’s when they develop moyamoya, where they have new blood vessels formed. The problem is whether these new blood vessels are more fragile and more at risk for hemorrhagic events. So patients with sickle cell are at an extreme risk for CNS events. They’re at risk early in life. It continues to progress, and it needs to be closely monitored for disease progression. The decreased oxygen delivery and compensatory increased cerebral blood flow is a major reason for CNS disease and is directly contributed to by the anemia.
Transcript edited for clarity.